Synthetic composition and method for treating irritable bowel syndrome

Abstract

The application relates to a method for treating a patient with irritable bowel syndrome (IBS), the method comprising administering to the patient one or more neutral human milk oligosaccharides (HMOs) selected from 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), difucosyllactose (DFL), lacto-N-fucopentaose I, lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), and combinations thereof.

What is claimed is: 
     
       1. A method comprising:
 selecting a non-infant human patient with irritable bowel syndrome (IBS) experiencing one or more IBS symptoms; 
 selecting an amount of one or more neutral human milk oligosaccharides (HMOs) selected from the group consisting of 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), difucosyllactose (DFL), lacto-N-fucopentaose I (LNFP-I), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), and combinations thereof, the amount effective for increasing a relative abundance of  Bifidobacterium adolescentis  in the gastrointestinal microbiota of the non-infant human patient; and 
 increasing the relative abundance of  Bifidobacterium adolescentis  in the gastrointestinal microbiota of the non-infant human patient and reducing the likelihood of the non-infant human patient experiencing the one or more IBS symptoms by administering a daily dose of the selected amount of the one or more neutral HMOs to the non-infant human patient, wherein the daily dose is from about 2.5 g to about 10 g. 
 
     
     
       2. The method of  claim 1 , wherein the non-infant human patient has undergone treatment with an antibiotic to reduce bacteria that negatively affect the IBS, and wherein the non-infant human patient has not consumed the antibiotic in a three-month period prior to the administering of the one or more neutral HMOs. 
     
     
       3. The method of  claim 1 , wherein the one or more IBS symptoms are chronic symptoms selected from the group consisting of abdominal pain, abdominal discomfort, abdominal bloating, change in bowel movement patterns, diarrhea, and constipation. 
     
     
       4. The method of  claim 1 , further comprising administering with the selected amount of the one or more neutral HMOs, one or more sialylated HMOs selected from the group consisting of 6′-sialyllactose (6′-SL) and 3′-sialyllactose (3′-SL). 
     
     
       5. The method of  claim 1 , wherein administering the one or more neutral HMOs comprises administering a mixture of:
 one or more fucosylated neutral HMOs selected from the group consisting of 2′-FL, 3-FL, DFL, and LNFP-I; and 
 one or more non-fucosylated neutral HMOs selected from the group consisting of LNT and LNnT. 
 
     
     
       6. The method of  claim 1 , wherein the mass ratio of the fucosylated neutral HMOs to the non-fucosylated neutral HMOs in the mixture is from 4:1 to 1:1. 
     
     
       7. The method of  claim 1 , further comprising administering the selected amount of the one or more neutral HMOs for an initial treatment period of from 1 week to 8 weeks. 
     
     
       8. The method of  claim 7 , further comprising, after the initial treatment period, administering a daily dose of from 1 g to 5 g of the one or more neutral HMOs for a maintenance period of at least 1 month. 
     
     
       9. A method comprising:
 selecting a non-infant human patient who has been previously treated for one or more symptoms of irritable bowel syndrome (IBS); 
 selecting an amount of one or more human milk oligosaccharides (HMOs) selected from the group consisting of 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), difucosyllactose (DFL), lacto-N-fucopentaose I (LNFP-I), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), and combinations thereof, the selected amount effective for increasing a relative abundance of  Bifidobacterium adolescentis  in the gastrointestinal microbiota of the non-infant human patient; and 
 increasing the relative abundance of  Bifidobacterium adolescentis  in the gastrointestinal microbiota of the non-infant human patient and reducing in the non-infant human patient a risk of re-occurrence of one or more symptoms associated with IBS by administering a daily dose of the amount of the one or more neutral HMOs and optionally one or more excipients, to the non-infant human patient, wherein the daily dose is from about 2.5 g to about 10 g. 
 
     
     
       10. The method of  claim 9 , wherein the non-infant human patient has undergone treatment with an antibiotic and wherein the non-infant human patient has not consumed the antibiotic in a three-month period prior to the administering of the one or more neutral HMOs. 
     
     
       11. The method of  claim 9 , further comprising reducing in the non-infant human patient the severity of one or more chronic symptoms selected from the group consisting of: abdominal pain, abdominal discomfort, abdominal bloating, changes in bowel movement patterns, diarrhea, and constipation, by administering the selected amount of the one or more neutral HMOs to the non-infant human patient. 
     
     
       12. The method of  claim 9 , further comprising reducing in the non-infant human patient the re-occurrence of one or more chronic symptoms selected from the group consisting of abdominal pain, abdominal discomfort, abdominal bloating, change in bowel movement patterns, diarrhea, and constipation, by administering the selected amount of the one or more neutral HMOs to the non-infant human patient. 
     
     
       13. The method of  claim 12 , further comprising administering with the selected amount of the one or more neutral HMOs, one or more sialylated HMOs selected from the group consisting of 6′-sialyllactose (6′-SL) and 3′-sialyllactose (3′-SL). 
     
     
       14. The method of  claim 9 , wherein administering the one or more neutral HMOs comprises administering a mixture of:
 one or more fucosylated neutral HMOs selected from the group consisting of 2′-FL, 3-FL, DFL, and LNFP-I; and 
 one or more non-fucosylated neutral HMOs selected from the group consisting of LNT and LNnT. 
 
     
     
       15. The method of  claim 9 , wherein a mass ratio of the fucosylated neutral HMOs to the non-fucosylated HMOs in the mixture is from 4:1 to 2:1. 
     
     
       16. The method of  claim 9 , further comprising administering the mixture of the one or more neutral HMOs for a treatment period of from 1 week to 8 weeks. 
     
     
       17. The method of  claim 9 , further comprising administering a daily dose of from 1 g to 5 g of the selected amount of the mixture of the one or more neutral HMOs for a maintenance period of at least 1 month. 
     
     
       18. A method comprising:
 selecting a non-infant human patient experiencing one or more symptoms of irritable bowel syndrome (IBS); 
 selecting an amount of one or more human milk oligosaccharides (HMOs) selected from the group consisting of 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), difucosyllactose (DFL), lacto-N-fucopentaose I, lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), and combinations thereof, the selected amount effective for increasing a relative abundance of  Bifidobacterium adolescentis  in the gastrointestinal microbiota of the non-infant human patient; and 
 increasing the relative abundance of  Bifidobacterium adolescentis  in the gastrointestinal microbiota of the non-infant human patient and reducing in the non-infant human patient the level of one or more inflammatory biomarkers or symptoms associated with the IBS by administering a daily dose of the selected amount of the one or more neutral HMOs to the non-infant human patient, wherein the daily dose is from about 2.5 g to about 10 g. 
 
     
     
       19. The method of  claim 18 , wherein the one or more inflammatory biomarkers associated with the IBS are selected from the group consisting of tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and lipopolysaccharide binding protein (LBP).